ArticleAntimicrobial agents and chemotherapy2014
A low-affinity penicillin-binding protein 2x variant is required for heteroresistance in Streptococcus pneumoniae.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Global trends and research profile of antibiotic heteroresistance: a bibliometric and visual analysis.Frontiers in microbiology · 2026Pooled it
- Phase-Specific Antibiotic Resistance Mechanisms in anbioRxiv : the preprint server for biology · 2025Article
- Biological puzzles solved by usingJournal of bacteriology · 2024Review
- Klebsiella pneumoniae peptide hijacks a Streptococcus pneumoniae permease to subvert pneumococcal growth and colonization.Communications biology · 2024Article
- Impact of Difluoromethylornithine and AMXT 1501 on Gene Expression and Capsule Regulation inBiomolecules · 2024Article
- Group A streptococcus isolated in Guyana with reduced susceptibility to β-lactam antibiotics.Access microbiology · 2024Article
- New Resistance Mutations Linked to Decreased Susceptibility to Solithromycin in Streptococcus pneumoniae Revealed by Chemogenomic Screens.Antimicrobial agents and chemotherapy · 2023Article
- Inducible Mega-Mediated Macrolide Resistance Confers Heteroresistance in Streptococcus pneumoniae.Antimicrobial agents and chemotherapy · 2023Article
- Phenotypic and Molecular Characterization of Carbapenem-HeteroresistantAntibiotics (Basel, Switzerland) · 2022Article
- Quorum sensing regulates heteroresistance inFrontiers in microbiology · 2022Article
- Mms19 promotes spindle microtubule assembly in Drosophila neural stem cells.PLoS genetics · 2020Article
- Mechanisms and clinical relevance of bacterial heteroresistance.Nature reviews. Microbiology · 2019Review
- Resistance formation to nitro drugs in Giardia lamblia: No common markers identified by comparative proteomics.International journal for parasitology. Drugs and drug resistance · 2019Article
- Nasal Resistome Development in Infants With Cystic Fibrosis in the First Year of Life.Frontiers in microbiology · 2019Article
- Foreign peptide triggers boost in pneumococcal metabolism and growth.BMC microbiology · 2018Article
- Peptide Ligands of AmiA, AliA, and AliB Proteins Determine Pneumococcal Phenotype.Frontiers in microbiology · 2018Article
- Substitutions in PBP2b from β-Lactam-resistantThe Journal of biological chemistry · 2017Article
- Physiological Roles of the Dual Phosphate Transporter Systems in Low and High Phosphate Conditions and in Capsule Maintenance of Streptococcus pneumoniae D39.Frontiers in cellular and infection microbiology · 2016Article
- FUS/TLS contributes to replication-dependent histone gene expression by interaction with U7 snRNPs and histone-specific transcription factors.Nucleic acids research · 2015Article
- Antimicrobial heteroresistance: an emerging field in need of clarity.Clinical microbiology reviews · 2015Review
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Heteroresistance to penicillin in Streptococcus pneumoniae is the ability of subpopulations to grow at a higher antibiotic concentration than expected from the MIC. This may render conventional resistance testing unreliable and lead to therapeutic failure. We investigated the role of the primary β-lactam resistance determinants, penicillin-binding protein 2b (PBP2b) and PBP2x, and the secondary resistance determinant PBP1a in heteroresistance to penicillin. Transformants containing PBP genes from the heteroresistant strain Spain(23F) 2349 in the nonheteroresistant strain R6 background were tested for heteroresistance by population analysis profiling (PAP). We found that pbp2x, but not pbp2b or pbp1a alone, conferred heteroresistance to R6. However, a change of pbp2x expression was not observed, and therefore, expression does not correlate with an increased proportion of resistant subpopulations. In addition, the influence of the CiaRH system, mediating PBP-independent β-lactam resistance, was assessed by PAP on ciaR disruption mutants but revealed no heteroresistant phenotype. We also showed that the highly resistant subpopulations (HOM*) of transformants containing low-affinity pbp2x undergo an increase in resistance upon selection on penicillin plates that partially reverts after passaging on selection-free medium. Shotgun proteomic analysis showed an upregulation of phosphate ABC transporter subunit proteins encoded by pstS, phoU, pstB, and pstC in these highly resistant subpopulations. In conclusion, the presence of low-affinity pbp2x enables certain pneumococcal colonies to survive in the presence of β-lactams. Upregulation of phosphate ABC transporter genes may represent a reversible adaptation to antibiotic stress.
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